Fig. 5: Lysosome-dependent lipolysis is operative in human adipose tissue with fasting.

a MiT/TFE factor fold change relative to day 0 from human transcriptomics analyses of subcutaneous adipose tissue during inpatient 10 day fast (n = 7). Differential expression using a linear model the likelihood ratio test against a reduced model that did not include the time factor (∼1) and with Benjamin-Hochberg multiple-test correction. b Two-sided Spearman correlation between TFEC fold change and LIPA fold change data-set in A (n = 7). c Two-sided Spearman correlation between MITF fold change and LIPA fold change data-set in A (n = 7). d Doxycycline-inducible targeting of lipolysis genes in adipocytes derived from human SGBS preadipocytes and subjected to nutrient restriction relative to scramble controls (shSCR). The dark gray bars with associated dashed lines denote non-nutrient restricted controls. One-way ANOVA/Dunnett’s. Each dot indicates the mean of technical replicates from n = 3 independent biological replicate experiments, and expressed as mean, S.D.M. NEFA=non-esterified fatty acids. e LIPA assessed by qPCR for knockdown experiments in F. Significance assessed with Friedman’s/Dunnett’s tests. Each dot indicates the mean of technical replicates from n = 3 independent biological replicate experiments, and expressed as mean, S.D.M. f Human adipose tissue explant culture and lipolytic response to nutrient restriction. Left=glycerol; right=NEFA. Pharmacologic inhibitors were used to assess lysosomal-dependent lipolysis (Bafilomycin, Lalistat2). Each dot indicates the mean of technical replicates from n = 4 independent biological replicate experiments, and expressed as mean, S.D.M. One-way ANOVA/Dunnett’s (glycerol) and Friedman’s/Dunnett’s tests (NEFA). Con=control. g Human adipose tissue explant culture and lipolytic response to in vitro adrenergic stimulus (catecholamines): left=glycerol; right=NEFA. Pharmacologic inhibitors were used to assess lysosomal-dependent lipolysis (Bafilomycin, Lalistat2). Each dot indicates the mean of technical replicates from n = 4 independent biological replicate experiments, and expressed as mean, S.D.M. Friedman’s/Dunnett’s tests. Con=control.